Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

The effect of mirabegron, used for overactive bladder treatment, on female sexual function: a prospective controlled study.

BACKGROUND: Αim of the study was to determine the effect of mirabegron, used for overactive bladder (OAB) treatment, on female sexual function. METHODS: Eighty five sexually active women suffering from overactive bladder were prospectively enrolled in this study. Females were divided into two groups. In Group A (control), 48 patients received no treatment and in Group B, 37 patients received mirabegron 50 mg/daily for 3 months. Patients were evaluated with FSFI-Gr at the beginning of the study and again after a period of 3 months. RESULTS: In Group B, there was a significant increase post-treatment compared to baseline (p < 0.001) in total FSFI (20.3 (3.8) to 26.6 (4.2)) and all domains (desire: 3.0 (1.2) to 4.8 (1.2)), arousal: 3.0 (0.8) to 4.8 (0.9), lubrication: 3.9 (1.1) to 4.8 (1.2), orgasm: 3.6 (0.8) to 4.8 (1.0), satisfaction: 3.2 (0.4) to 4.0 (0.8) and pain: 3.2 (0.8) to 4.4 (1.2)). In Group A, there were no statistically significant changes in pre- and post-observation values. CONCLUSIONS: This study is one of the few demonstrating that management of OAB with mirabegron improves female sexual function. TRIAL REGISTRATION: TRN ISRCTN17199301 , 20/10/2017, retrospectively registered.

Antioxidant treatment ameliorates diabetes-induced dysfunction of the vas deferens in a rat model.

Diabetes mellitus (DM) affects the male ejaculatory function. This study was designed to evaluate the role of oxidative stress in the development of diabetes-induced dysfunction of vas deferens (VD) in the rat. DM was induced by streptozotocin in 40 male Wistar rats. Subsequently, the diabetic animals were divided into three groups: DM group, DM + Eda group and DM + Tau group. These groups were administered saline, edaravone and taurine, respectively, daily for 4 weeks. Another group of ten rats served as a control group. DM was diagnosed in the 40 streptozotocin-injected rats. DM significantly reduced the VD weight. Additionally, DM induced in vitro VD hypercontractility, VD histological abnormalities and increased the serum and VD tissue concentration of malondialdehyde. VD immunohistochemistry revealed overexpression of three markers of oxidative stress. DM significantly reduced serum testosterone levels. No live birth was documented in all DM rats in mating experiments. Antioxidants significantly improved all the aforementioned parameters, except the testosterone levels. This study indicates a deleterious impact of DM-induced oxidative stress on VD histological and functional features. Antioxidant treatment may provide an adjunct tool to alleviate ejaculatory disorders for male patients with type 1 diabetes.

Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent.

This study investigated the hypothesis that genetic alterations of the human insulin-like 3 (INSL3) gene are associated with testicular maldescent (TMD). Genomic DNA was extracted and amplified from peripheral blood samples of 170 unrelated children with all possible phenotypical expressions of TMD and 50 volunteers with normal external genitalia from the general paediatric population (controls). PCR-single strand conformation polymorphism analysis was used to screen INSL3 gene for genetic variants. For rapid screening of a detected nonsilent genetic alteration, restriction assay using endonuclease Eag I was further employed. Products were analysed on 2% agarose gel and restriction patterns were visualised by ethidium bromide. Differences in genotype and allelic distributions of nonsilent genetic alterations were evaluated between (i) patients-controls, (ii) familial-sporadic, (iii) bilateral-unilateral and (iv) intra-abdominal-inguinal cases of TMD. No mutations were detected. Three common INSL3 gene polymorphisms (27G>A, 126G>A, 178G>A) unrelated to any particular phenotype of TMD were detected both in patients and controls. These results indicate that INSL3 gene mutations are not a common cause of TMD in the human.

The (TAAAA)n polymorphism of sex hormone-binding globulin gene is not associated with testicular maldescent.

The aim of this family-based study was to investigate the potential association/genetic linkage of the (TAAAA)n polymorphism of sex hormone-binding globulin gene proximal promoter with testicular maldescent (TMD). Genomic DNA was extracted from the peripheral blood of 487 subjects (174 index families): (i) 180 children with all phenotypes of TMD, (ii) 307 parents (156 mothers and 151 fathers). Conventional polymerase chain reaction amplification products were electrophoresed on 10% nondenaturating polyacrylamide gel and visualised by silver staining. After excluding ambiguous parental-child trios and most cases of index families with missing parental genotypes, 429 individuals were left for analysis: 138 completely typed nuclear families (five included a second affected child) and five child-parent couples (one parent missing). Eight fathers presented history of TMD, that is, a total of 156 cases with TMD were analysed. Alleles were analysed with the affected family-based control method and logistic regression-based extension of the transmission disequilibrium test for multiallelic loci. (ΤΑΑΑΑ)n polymorphism analysis revealed six alleles based on repeat numbers (n=5-10). No association/genetic linkage between the (TAAAA)n polymorphism and TMD was detected. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Synergistic effect of follicle-stimulating hormone receptor and androgen receptor gene variants on semen quality.

Follicle-stimulating hormone (FSH), interacting with its receptor (FSHR), participates in the production of spermatozoa and androgens. Androgens exert their effects on male sex determination, development and sperm production by binding to androgen receptor (AR). In the present study, we sought to explore the potential synergistic effects of FSHR and AR gene variants on sperm quality. 200 oligozoospermic and 250 normozoospermic men were examined. DNA was extracted from spermatozoa, and the FSHR 307 (T/A), FSHR 680 (N/S) and AR (CAG)n polymorphisms were genotyped. Their parallel analysis revealed six combined genotypes. A gradual reduction of sperm motility, from long AR allele-Thr307Thr/Asn680Asn carriers to long AR allele-Ala307Ala/Ser680Ser carriers and from short AR allele-Thr307Thr/Asn680Asn carriers to short AR allele-Ala307Ala/Ser680Ser carriers was revealed in normozoospermic men (P < 0.001). Similar associations were observed in oligozoospermic men (P < 0.001). In our series, the synergism of the long AR alleles with the FSHRThr307/Asn680 allelic variant was associated with increased sperm motility, while the synergism of the short AR alleles with the FSHRAla307/Ser680 allelic variant was associated with decreased motility, supporting the significance of these genes in semen quality.

Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent.

The aim of the study was to investigate the hypothesis that Y chromosome microdeletions are directly implicated in testicular maldescent. Genomic DNA was extracted from the peripheral blood of 292 subjects. This population consisted of (i) 180 children with all phenotypes of isolated (non-syndromic) testicular maldescent from 174 index families, (ii) affected adult relatives available (n = 12) and (iii) 100 unrelated children with normal external genitalia (controls). The sequence-tagged site primer set and the conditions of conventional polymerase chain reaction amplification were based on the current laboratory guidelines for molecular diagnosis of Y chromosome microdeletions recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Two multiplex reactions were designed to screen the regions of azoospermic factors a, b and c. Each multiplex reaction included adequate internal and external amplification controls. Amplification products were submitted to electrophoresis on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h and visualised under ultraviolet light. No microdeletions were detected in any subject. These results indicate that Y chromosome microdeletions are not directly implicated in the pathogenesis of testicular maldescent. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Semen quality is influenced by androgen receptor and aromatase gene synergism.

STUDY QUESTION: Does synergism between AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms influence the quality of sperm? SUMMARY ANSWER: AR(CAG)(n) and CYP19(TTTA)(n) polymorphisms had a synergistic effect on sperm concentration and motility. WHAT IS KNOWN ALREADY: Androgens exert their action in the testicular tissue by binding to androgen receptor (AR), while their action is mediated by the aromatase P450 enzyme (CYP19). AR(CAG)(n) alleles are associated with sperm motility and CYP19(TTTA)(n) allelic variants have implications for sperm concentration and motility. STUDY DESIGN, SIZE, DURATION: Two hundred oligozoospermic and 250 normozoospermic men who presented for infertility investigation were examined during a period of 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conventional semen analysis was performed. DNA was extracted from spermatozoa and both polymorphisms were genotyped by polymerase chain reaction. Serum hormone levels were determined. MAIN RESULTS AND THE ROLE OF CHANCE: Six combined genotypes were identified between the 18 AR(CAG)(n) alleles with 12-32 repeats and the 6 CYP19(TTTA)(n) alleles with 7-12 repeats. A gradual reduction in the sperm concentration (10(6)/ml) and motility (%) from long AR allele-non-CYP19(TTTA)(7) allele carriers to long AR allele-CYP19(TTTA)(7) homozygotes and from short AR allele-non-CYP19(TTTA)(7) carriers to short AR allele-CYP19(TTTA)(7) homozygotes was observed in normozoospermic men (means ± SD; concentration: 93 ± 53.1 versus 65 ± 48.6 and 85 ± 60.1 versus 37 ± 17.2l, P < 0.002; motility: 63 ± 10.3 versus 55 ± 14.5 and 52 ± 19.6 versus 41 ± 13.7, P < 0.001, respectively). Similar associations were observed in oligozoospermic men (concentration: 10 ± 4.2 versus 9 ± 5.9 and 10 ± 6.3 versus 6 ± 3.1, P < 0.03; motility: 47 ± 17.1 versus 39 ± 6.2 and 39 ± 22 versus 27 ± 18.3, P < 0.003, respectively). The above associations of the combined genotypes with sperm concentration and motility were confirmed in the total study population (P < 0.006 and P < 0.001, respectively). LIMITATIONS, REASONS FOR CAUTION: Our study population was limited to Greek Caucasian adult males, residents of Northwest Greece. WIDER IMPLICATIONS OF THE FINDINGS: The confirmation of our findings in other populations would verify the significance of AR and CYP19 genes for spermatogenesis. STUDY FUNDING/COMPETING INTERESTS: This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. The authors declare no conflicts of interest.

Mitigation of methane production from cattle by feeding cashew nut shell liquid.

The effects of cashew nut shell liquid (CNSL) feeding on methane production and rumen fermentation were investigated by repeatedly using 3 Holstein nonlactating cows with rumen fistulas. The cows were fed a concentrate and hay diet (6:4 ratio) for 4 wk (control period) followed by the same diet with a CNSL-containing pellet for the next 3 wk (CNSL period). Two trials were conducted using CNSL pellets blended with only silica (trial 1) or with several other ingredients (trial 2). Each pellet type was fed to cows to allow CNSL intake at 4 g/100 kg of body weight per day. Methane production was measured in a respiration chamber system, and energy balance, nutrient digestibility, and rumen microbial changes were monitored. Methane production per unit of dry matter intake decreased by 38.3 and 19.3% in CNSL feeding trials 1 and 2, respectively. Energy loss as methane emission decreased from 9.7 to 6.1% (trial 1) and from 8.4 to 7.0% (trial 2) with CNSL feeding, whereas the loss to feces (trial 1) and heat production (trial 2) increased. Retained energy did not differ between the control and CNSL periods. Digestibility of dry matter and gross energy decreased with CNSL feeding in trial 1, but did not differ in trial 2. Feeding CNSL caused a decrease in acetate and total short-chain fatty acid levels and an increase in propionate proportion in both trials. Relative copy number of methyl coenzyme-M reductase subunit A gene and its expression decreased with CNSL feeding. The relative abundance of fibrolytic or formate-producing species such as Ruminococcus flavefaciens, Butyrivibrio fibrisolvens, and Treponema bryantii decreased, but species related to propionate production, including Prevotella ruminicolla, Selenomonas ruminantium, Anaerovibrio lipolytica, and Succinivibrio dextrinosolvens, increased. If used in a suitable formulation, CNSL acts as a potent methane-inhibiting and propionate-enhancing agent through the alteration of rumen microbiota without adversely affecting feed digestibility.

Dramatic reduction in sperm parameters following bariatric surgery: report of two cases.

Severe obesity constitutes the main public health crisis of the industrialised world. Bariatric surgery has been proposed as the most efficient treatment of obesity. In this study, we report the potential effects of bariatric surgery on semen parameters in male partners of couples undergoing assisted reproduction. These patients had been tested in the context of infertility treatment in two consecutive cycles before and after bariatric surgery. A marked reduction in sperm parameters was observed in a period of twelve to eighteen months after surgery. This unfavourable effect had also remarkable effects on the assisted reproduction outcome, necessitating the counselling of patients before bariatric surgery.

Effects of phosphodiesterase-5 inhibitor vardenafil on testicular androgen-binding protein secretion, the maintenance of foci of advanced spermatogenesis and the sperm fertilising capacity in azoospermic men.

We evaluated the effects of vardenafil on testicular androgen-binding protein secretion (ABP). Bilaterally obstructed azoospermic (OA)-men (n = 19) (group A) underwent unilateral testicular biopsy. A group of nonobstructed azoospermic (NOA)-men (n = 68) (group B) underwent bilateral testicular biopsy. ABP secretion in vitro by testicular tissue was assessed in each participant of every group. In addition, intracytoplasmic sperm injection (ICSI) cycles were performed in several couples of group A or group B using frozen/thawed spermatozoa from the biopsy material. Ten OA-men (group A1), 14 NOA-men (group B1), and nine different NOA-men (group B2) had been positive for spermatozoa in the biopsy but pregnancies were not achieved in the respective female partners. Men of groups A1, B1 and B2 were treated with vardenafil, vardenafil and L-carnitine respectively. Then, the men of groups A1, B1 and B2 underwent a second testicular (unilateral) biopsy. Within the group A1 and within the group B1, ABP secretion rate was significantly larger after vardenafil treatment than prior to vardenafil treatment. In addition, fertilisation rates in ICSI cycles within groups A1 or B1 were not affected by vardenafil administration. Vardenafil administration in NOA-men increased ABP secretion and did not affect detrimentally the presence of testicular foci of advanced spermatogenesis.

Synthesis and pigmental properties of titanium phosphates with the addition of urea.

As a white pigment, titanium oxide is used for cosmetic application. This oxide is well known to have the photo catalytic activity. Therefore, a certain degree of sebum is decomposed by the ultraviolet radiation in the sunlight. In this work, titanium phosphates were prepared as a novel white pigment. Their chemical composition, powder properties, photo catalytic activity, moisture retention and smooth were studied with the addition of urea. These white pigments had little photo catalytic activity. The addition of urea improved the moisture retention of titanium phosphates. The slipping resistance of samples became small by heating, on the other hand, the roughness of samples became small by the addition of urea.

Gynecomastia as a first clinical sign of nonseminomatous germ cell tumor.

INTRODUCTION: Gynecomastia is a common clinical sign in several diseases. In this report we present a case of gynecomastia with underlying testicular tumor which remained misdiagnosed for a prolonged period of time. CASE REPORT: A 16-year-old adolescent noticed unilateral painless swelling of the left breast. He was referred to the Department of General Surgery and examined by a breast surgeon. A diagnosis of mastitis was made and a treatment with an oral antibiotic drug began. After failure of the initial antibiotic treatment, the patient was referred to the Department of Endocrinology and left testicular cancer was diagnosed. Unilateral high inguinal orchidectomy and subsequent chemotherapeutic treatment were performed. CONCLUSION: Primary care physicians should be aware of the possibility of a concomitant presence of gynecomastia and testicular cancer. We suggest a physical examination as well as a laboratory investigation, and testicular ultrasonography of the testes in all patients with gynecomastia.

Phylogenetic diversity of gene sequences isolated from the rumen as analysed using a self-organizing map (SOM).

AIMS: To determine the origins of DNA sequences isolated from the rumen microbial ecosystem using a self-organizing map (SOM). METHODS AND RESULTS: DNA sequences other than 16S small subunit ribosomal RNA (SSU rRNA) gene sequences that were detected from the rumen were analysed by the SOM method reported by Abe et al. [2000, Self-Organizing Map (SOM) unveils and visualizes hidden sequence characteristics of a wide range of eukaryote genomes. Gene 365, 27-34]. Because query sequences positioned by SOM were scattered on the master drawing of SOM, it was suggested that many DNA sequences isolated from the rumen were collected from a broad range of micro-organisms. Although the results obtained by SOM were similar to those obtained by the neighbour-joining (NJ) method, SOM was able to presume the phylotypes of the query sequences without information about the 16S SSU rRNA gene sequences and homology searches, and to reveal existence of novel micro-organisms deduced to be cellulolytic bacteria, archaea and methanotrophic bacterium. CONCLUSIONS: As the SOM method defined phylotypes of unreported rumen micro-organisms, it is presumed that these phylotypes would be involved in rumen fermentation in cooperation with known rumen micro-organisms. Moreover, it is demonstrated that SOM is a useful tool for affiliating DNA sequences, which have no matches in databases. SIGNIFICANCE AND IMPACT OF STUDY: Through SOM analysis, a better means of identifying rumen micro-organisms and estimating their roles in rumen function was provided.

Difference in the nature of tannins on in vitro ruminal methane and volatile fatty acid production and on methanogenic archaea and protozoal populations.

Six plant sources of hydrolyzable tannins (HT) or HT and condensed tannins (CT; designated as HT1, HT2, HT3, HT + CT1, HT + CT2, and HT + CT3) were evaluated to determine their effects in vitro on CH(4) production and on ruminal archaeal and protozoa populations, and to assess potential differences in biological activities between sources containing HT only or HT and CT. Samples HT1, HT2, and HT3 contained only HT, whereas samples HT + CT1, HT + CT2, and HT + CT3 contained HT and CT. In experiment 1, in vitro incubations with samples containing HT or HT + CT resulted in a decrease in CH(4) production of 0.6 and 5.5%, respectively, compared with that produced by incubations containing the added tannin binder polyethylene glycol-6000. Tannin also suppressed the population of methanogenic archaea in all incubations except those with HT2, with an average decrease of 11.6% in HT incubations (15.8, 7.09, and 12.0 in HT1, HT2, and HT3) and 28.6% in incubations containing HT + CT (35.0, 40.1, and 10.8 in HT + CT1, HT + CT2, and HT + CT3) when compared with incubations containing added polyethylene glycol-6000. The mean decrease in protozoal counts was 12.3% in HT and 36.2% in HT + CT incubations. Tannins increased in vitro pH, reduced total VFA concentrations, increased propionate concentrations, and decreased concentrations of iso-acids. In experiment 2, when a basal diet was incubated with graded levels of HT + CT1, HT + CT2, and HT + CT3, the total gas and CH4 production and archaeal and protozoal populations decreased as the concentration of tannins increased. Our results confirm that tannins suppress methanogenesis by reducing methanogenic populations in the rumen either directly or by reducing the protozoal population, thereby reducing methanogens symbiotically associated with the protozoal population. In addition, tannin sources containing both HT and CT were more potent in suppressing methanogenesis than those containing only HT.

[Surgical treatment for the second double lung cancers following chemotherapy for small cell lung cancer].

We report a case with surgery for the 2nd primary double lung cancers-adenocarcinoma and squamous cell carcinoma which developed in the right upper lobe after 5 years successful control by chemotherapy for small cell lung cancer in the left upper lobe. Long term survivors with small cell lung cancer have recently increased as a result of progress of chemotherapy. Therefore, 2nd primary lung cancer is not rare after the treatment for the initial small cell lung cancer. Although several causes have been proposed on the development of 2nd primary lung cancer after small cell lung cancer treatment, smoking history was strongly suggested as a cause in this case. Careful follow-up especially focusing on 2nd primary lung cancer development is necessary for patients after successful treatment for small cell lung cancer.

Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Synchronous occurrence of intraductal papillary mucinous neoplasm (IPMN) and ductal carcinoma of the pancreas has been reported. Branch duct IPMNs with lower likelihood of malignancy are not submitted to resection but are followed-up, so ductal carcinoma may develop during the follow-up. The development of ductal carcinoma of the pancreas during follow-up of branch duct IPMNs was investigated. METHODS: 60 patients with branch duct IPMN who had an intraductal tumour of <10 mm on imaging examinations and a negative result for malignancy on cytological examination of the pancreatic juice were investigated. They were followed-up mainly by ultrasonography (US), and additionally by endoscopic ultrasonography (EUS), CT, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) with cytological examination of the pancreatic juice for an average period of 87 months. RESULTS: Ductal carcinoma of the pancreas distinct from IPMN developed in 5 of 60 (8%) branch duct IPMNs during follow-up. The 5-year rate of development of ductal carcinoma was 6.9% (95% CI 0.4% to 13.4%), the incidence of ductal carcinoma was 1.1% (95% CI 0.1% to 2.2%) per year and the standardised incidence ratio of development of ductal carcinoma was 26 (95% CI 3 to 48). Patients >70 years old developed ductal carcinoma significantly more frequently than those under 69. Four of five ductal carcinomas identified during follow-up were resectable. Cancer developed in IPMN in 2 of 60 (3%) branch duct IPMNs during follow-up. CONCLUSIONS: During follow-up of branch duct IPMNs, ductal carcinoma of the pancreas not infrequently developed distinct from IPMN. In the follow-up of IPMN, special attention should be paid to the development of ductal carcinoma of the pancreas.

The detection of possible sensor histidine kinases regulating citrate/malate metabolism from the bovine rumen microbial ecosystem.

AIMS: To detect sensor histidine protein kinases (HPKs) similar to accessory gene regulator C (AgrC) from the rumen microbial ecosystem. METHODS AND THE RESULTS: Genes related to sensor HPKs were amplified by PCR using two pairs of agrC-specfic primers from DNA extracted from bovine rumen contents. The PCR products were cloned, sequenced and phylogenetically analysed. It appeared that two sequences were HPKs. CONCLUSIONS: Although amino acid sequences deduced from the nucleotide sequences obtained in this study showed high similarities with sensor HPKs responding to citrate or C(4)-dicarboxylates, they did not show high similarities with AgrC. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed the presence in the rumen of sensor HPKs responding to citrate or C(4)-dicarboxylates, which could stimulate rumen fermentation. Therefore, it has been shown that citrate or C(4)-dicarboxylate metabolism is partially regulated by a two-component regulatory system in some rumen bacteria.